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Canine Protein Losing Enteropathies Willard, M Canine Protein Losing Enteropathies Willard, M. Texas A&M University, Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Texas, USA. * Corresponding Author: Dr. Michael Willard, DVM, DACVIM. College of Veterinary Medicine, Department of Small Animal Clinical Sciences, TAMU- 4474, Texas A&M University, College Station, TX 77843-4474, USA. Email: [email protected] ABSTRACT Protein-losing enteropathies are traditionally thought of as being diseases with a very poor prognosis. While this is often true, there are subsets of these patients which, if diagnosed in a timely fashion, may often have a relatively good prognosis. Lymphangiectasia in particular is a disease that is often misdiagnosed or diagnosed so late that it is no longer treatable. Clinicians should actively seek for evidence of lymphangiectasia in dogs with protein-losing enteropathies as this can be a disease that they may be able to control for years, at least in some cases. Keywords: Canine; Lymphangiectasia; Hypoalbuminemia; Diagnosis REVIEW may lose over half of their plasma proteins and consequently While relatively uncommon in human medicine, protein- have normal serum globulin concentrations. Conversely, losing enteropathies (PLE) are actually relatively common in occasional panhypoproteinemic dogs have hepatic disease dogs (1). Historically, they have tended to be associated with or glomerular disease as the major source of protein loss, severe diseases, and were considered to have a poor prognosis. for reasons which are not clear. Therefore, the work up for (2) However, new data suggests that there is a subset of these hypoalbuminemic dogs is the same regardless of whether or animals that can actually respond reasonably well to therapy not they are panhypoproteinemic. and consequently enjoy a near normal life. For the patient with a serum albumin < 2 gm/dl, the Anytime the clinician is confronted with a hypoprotein- first step is to examine the skin for obvious lesions which emic dog, the first step is to measure the serum albumin con- could cause protein loss. Cutaneous lesions sufficient to cause centration as opposed to being satisfied with the serum total such hypoalbuminemia should be very obvious. The clinician protein concentration. It is important not to use a human should be able to simply examine the patient and quickly clinical pathology laboratory for this measurement as their ascertain whether or not the skin is the reason for the hypo- technology may or may not detect canine albumin. Normal albuminemia. Following this, hepatic function testing (e.g., dogs can have measured serum albumin concentrations of 1.5 resting and post-prandial serum bile acid concentrations) and gm/dl because of methodological problems with the human a urinalysis are indicated. If there is any doubt concerning technology when trying to measure canine albumin. In ad- the urinalysis results, then a urine protein:creatinine ratio dition, serum albumin is a bit of a “delicate” test to run. It is will quantify the magnitude of urinary protein loss. Severe clearly best to have the same veterinary laboratory measure hypoalbuminemia (i.e., < 2 gm/dl) in a dog with diarrhea the serum albumin each time so that one can accurately suggests a PLE; however, diarrhea (even severe diarrhea) compare values run on different days. can be due to primary hepatic disease. Many dogs and cats Panhypoproteinemia is not a very reliable indicator with PLE do not have vomiting or diarrhea, and some dogs of PLE. Dogs with PLE that initially were hyperglobulinemic with PLE present with only ascites. In fact, some dogs with Israel Journal of Veterinary Medicine Vol. 70 (3) September 2015 Protein Losing Enteropathies 17 Review Articles PLE will be fortuitously diagnosed when the dog comes in be intestinal lymphangiectasia, alimentary tract lymphoma for a routine yearly wellness check and has routine blood (LSA), fungal infections (i.e., histoplasmosis and pythiosis), examination. and then inflammatory bowel disease (IBD) (1). Other The serum cholesterol concentration can help the causes may include alimentary tract ulceration/erosion, clinician determine the cause of the hypoalbuminemia. severe disease of intestinal crypts, antibiotic-responsive en- Hypocholesterolemia concurrent with hypoalbumin- teropathy, and parasites. The major causes of PLE in juvenile emia suggests either PLE or hepatic insufficiency. dogs tend to be parastic and chronic intussusception. Cats Hypercholesterolemia occurring along with hypoalbumin- with PLE usually have IBD or alimentary tract lymphoma. emia is more suggestive of a protein-losing nephropathy. Once PLE has been diagnosed, intestinal biopsy is usually After severe, exudative cutaneous disease, protein-losing the best and more reliable means of determining the cause. nephropathy, and hepatic insufficiency are eliminated, then Biopsy can be performed via laparotomy, laparoscopy, or PLE is a reasonable tentative diagnosis of exclusion in pa- endoscopy. Feeding a small, fatty meal (use canned food, tients with a serum albumin < 2.0 gm/dl. Fecal concentra- not dry, and add in cream or corn oil) the night before the tions of alpha-1 protease inhibitor can be measured to try procedure might make it easier to diagnose lymphangiectasia to confirm PLE if there is confusion because of concurrent on histopathology (5). Flexible endoscopy, when done by hepatic or renal disease; however, this is not always an easy someone well trained in taking and submitting diagnostic test to run or interpret (3, 4). The major use for this test in tissue samples is usually more than adequate to obtain a solid clinical medicine seems to be the hypoalbuminemic patient in diagnosis. which one strongly suspects PLE (e.g., based upon it having However, it is preferable to image the dog before biopsy. severe diarrhea or having hypocholesterolemia), but which Radiographs and barium series are seldom useful. Abdominal also has a protein-losing nephropathy and/or hepatic disease. ultrasound is appropriate to make sure that there are no focal There are several nuances about this test, especially collecting infiltrates that are out of reach of the endoscope, or which samples that make it potentially difficult to interpret. This test might be more easily diagnosed by ultrasound-guided fine is seldom needed in clinical practice. needle aspiration. Furthermore, there are ultrasonographic Many dogs with PLE have relatively severe alimen- changes (i.e., hyperechoic streaks in the submucosa) that can tary tract disease (or at least alimentary tract disease that be diagnostic of lymphangiectasia (and thus eliminate the can become life-threatening) which should be diagnosed need for biopsy) (6). Feeding fat the night before the ultra- promptly to maximize the chance for successful therapy. sound can enhance the chances of ultrasound finding dilated Hence, aggressive diagnostics are typically an appropriate lymphatics in the submucosa, a finding that is considered vir- recommendation. Although therapeutic trials can be chosen tually diagnostic of lymphangiectasia. (7) Lymphangiectasia in place of classic diagnostic tests in many of the more com- can be relatively localized in one segment of the intestines. In mon alimentary tract diseases (e.g., dietary allergy, dietary many cases, lymphangiectasia, IBD or LSA may be obvious intolerance, antibiotic-responsive enteropathy, parasites), such in the ileum but not in the duodenum. Therefore, if flexible an approach is generally ill-advised if the serum albumin endoscopy will be done, it is important to biopsy both the concentration is less than 2.0 g/dl. This is true because it duodenum and ileum (8, 9). It is not necessary to enter the may be necessary to perform an antibiotic and/or dietary ileum with the endoscope to obtain a good tissue sample of therapeutic trial for 3-6 weeks in order to ascertain if it is the ileal mucosa. One can blindly pass the biopsy forceps being effective, and a patient with severe PLE can markedly through the ileocolic valve and typically obtain high quality deteriorate during this time, especially if the serum albumin mucosal biopsies of the ileum. concentration is falling rapidly. While histopathology is obviously the desired means of Any GI disease can cause PLE if it is severe enough. diagnosis, surgeons can sometimes make a tentative diagnosis Many acute gastrointestinal (GI) diseases cause PLE (e.g., of lymphangiectasia based upon grossly visible endoscopic parvoviral enteritis); however, these diseases typically are findings (i.e., numerous, erratic, grossly engorged lacteals comparatively easier to treat than the chronic GI disease seen as large white blebs on the mucosa) (10). However, causing PLE. The major causes of PLE in adult dogs tend to these lesions are “fragile” and apparently may be destroyed 18 Willard, M. Israel Journal of Veterinary Medicine Vol. 70 (3) September 2015 Review Articles during biopsy if the endoscopist or surgeon is not careful. homemade diets that are highly digestible and ultra-low in Furthermore, if one biopsies the intestines and cannot find a fat (e.g., white turkey meat plus potato or rice) or feeding cause of PLE, sometimes lymphangiectasia can be tentatively commercial diets is often very helpful in these patients. diagnosed by the process of eliminating all the other causes Commercial low fat diets can be used very successfully, but (e.g., IBD, lymphoma, parasites, intussusception, fungal they need to have the lowest possible fat content while at the infections,
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